IRON ASSIMILATION BY PATHOGENIC NEISSERIA SPP

致病性奈瑟菌对铁的同化作用

• 批准号: 3145820
• 负责人: Caroline A Genco
• 金额: $ 13.02万
• 依托单位: MOREHOUSE SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-09-30 至 1996-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3145820
• 关键词: Escherichia coli; Neisseria gonorrhoeae; Neisseria meningitidis; binding proteins; biological models; crosslink; formaldehyde; genetic promoter element; genetic transcription; hemoglobin; iron; iron metabolism; laboratory mouse; lactoferrin; microorganism metabolism; molecular cloning; mutant; nucleic acid probes; site directed mutagenesis; transferrin; transposon /insertion element; western blottings

The sites colonized by Neisseria gonorrhoeae and Neisseria meningitidis within the human host are diverse and each site represents a unique niche with respect to nutrients, environmental factors and competing microorganisms. The growth environment has a marked effect on the metabolism and cellular composition of N. gonorrhoeae and N. meningitidis, and an altered cellular composition is often reflected in the interaction of these microorganisms with the human host. The overall goal of this project is to elucidate the specific mechanisms employed by the pathogenic Neisseria for the assimilation of the essential nutrient iron. We will focus a majority of our efforts on the major iron- regulated protein, Fep. The recently cloned fep will allow us to create mutants defective in the production of Fep by miniT13 mutagenesis. We will examine the DNA sequences 5' to the fep structural gene and investigate how iron regulates the expression of Fep. We will also examine the regulation by iron of the Fep transcript. The specific location of the gonococcal Fep in the cell will be determined by osmotic shock techniques, as well as its interaction with other cellular components by cross-linking techniques. Finally, we will use our recently described N. meningitidis Tn916 mutagenesis system to isolate specific mutants defective in iron utilization. The resulting mutated DNA will be used as probes to clone the corresponding wildtype DNA. Mutants generated in these studies will be examined in vivo in our animal models. The mouse subcutaneous chamber model will be employed for studies on the growth of N. gonorrhoeae and N. meningitidis mutants. In addition, we will examine N. meningitidis mutants in the mouse bacteremia model. These studies will allow us to evaluate the role of iron utilization in the growth and subsequent pathogenicity of infection caused by N. gonorrhoeae and N. meningitidis.

淋病奈瑟菌和脑膜炎奈瑟菌定植的部位